Regional remodeling strain and its association with myocardial apoptosis after myocardial infarction in an ovine model

ObjectiveProgressive left ventricular remodeling after myocardial infarction has been viewed as an important contributor to progressive heart failure. The objective of this study was to investigate the relationship between myocardial apoptosis and strain during progressive cardiac remodeling.MethodsBefore creation of an anterolateral left ventricular infarction by ligation of diagonal arteries, 16 sonomicrometry transducers were placed in the left ventricular free wall of 8 sheep to assess regional deformation in the infarct, adjacent, and normally perfused remote myocardial regions over 8 weeks' duration. Hemodynamic, echocardiographic and sonomicrometric data were collected before infarction and then 30 minutes and 2, 6, and 8 weeks after infarction. At the end of the study, regional myocardial tissues were collected for apoptotic signaling proteins.ResultsAt terminal study, an increase in left ventricular end-diastolic pressure of 8.1 ± 0.1 mm Hg, a decrease in ejection fraction from 54.19% ± 5.68% to 30.55% ± 2.72%, and an end-diastolic volume increase of 46.08 ± 5.02 mL as compared with the preinfarct values were observed. The fractional contraction at terminal study correlated with the relative abundance of apoptotic protein expressions: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.27, P < .05), caspase-3 (r2 = 0.31, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.30, P < .05). These myocardial apoptotic activities also correlated with remodeling strain: cytochrome c (r2 = 0.02, P < .05), mitochondrial Bax (r2 = 0.28, P < .05), caspase-3 (r2 = 0.43, P < .05), and poly (adenosine diphosphate–ribose) polymerase (r2 = 0.37, P < .05).ConclusionIncrease in regional remodeling strain led to an increase in myocardial apoptosis and regional contractile dysfunction in heart failure

Surgical treatment of ischemic mitral regurgitation might not influence ventricular remodeling

ObjectivesSurgical treatment for ischemic mitral regurgitation has become more aggressive. However, no clinical study has demonstrated that surgical correction of chronic ischemic mitral regurgitation improves survival. We used 4 well-developed ovine models of postinfarction left ventricular remodeling to test the hypothesis that ischemic mitral regurgitation does not significantly contribute to postinfarction left ventricular remodeling.MethodsInfarction of 21% to 24% of the left ventricular mass was induced by means of coronary ligation in 77 sheep. Infarctions varied only by anatomic location in the left ventricle: anteroapical, n = 26; anterobasal, n = 16; laterobasal, n = 9; and posterobasal, n = 20. Six additional sheep had ring annuloplasty before posterobasal infarction. End-systolic and end-diastolic left ventricular volume, end-systolic muscle-to-cavity area ratio, left ventricular sphericity, ejection fraction, and degree of ischemic mitral regurgitation, as determined by means of quantitative echocardiography, were assessed before infarction and at 2, 5, and 8 weeks after infarction.ResultsAll infarcts resulted in significant postinfarction remodeling and decreased ejection fraction. Anteroapical infarcts lead to left ventricular aneurysms. Only posterobasal infarcts caused severe and progressive ischemic mitral regurgitation. Remodeling because of posterobasal infarcts was not more severe than that caused by infarcts at other locations. Furthermore, prophylactic annuloplasty prevented the development of mitral regurgitation after posterobasal infarction but had no effect on remodeling.ConclusionThe extent of postinfarction remodeling is determined on the basis of infarct size and location. The development of ischemic mitral regurgitation might not contribute significantly to adverse remodeling. Ischemic mitral regurgitation is likely a manifestation rather than an important impetus for postinfarction remodeling

Influence of inotropy and chronotropy on the mitral valve sphincter mechanism.

BACKGROUND: This study was designed to isolate and quantify the effects of ventricular inotropic and chronotropic state on the normal mitral valve annular sphincter mechanism. METHODS: Sonomicrometry tansducers were placed around the mitral annulus in six sheep; atrial pacing wires were also placed. One week later, esmolol was titrated to produce a baseline hemodynamic state with a heart rate of 90 bpm; hemodynamic and sonomicrometry data were recorded. Then animals were paced at 120 bpm and 150 bpm; data were recorded at each heart rate. Isoproterenol infusion was titrated to achieve a heart rate, without pacing, of 120 and 150 bpm; again, data were recorded. Annular area was calculated at end diastole (ED) and end systole (ES) for all experiments using sonomicrometry array localization. Analysis of variance was used to assess the independent effects of heart rate and inotropic state on annular area. RESULTS: Atrial pacing at 120 bpm produced ES and ED annular areas of 777 +/- 150 mm(2) and 748.8 +/- 140.1 mm(2), respectively. At the same heart rate, isoproterenol-treatment resulted in significantly smaller ES and ED areas: 699 +/- 160 mm(2) and 641.9 +/- 156.5 mm(2), respectively. Atrial pacing at 150 bpm produced ES and ED annular areas of 745.2 +/- 131.3 mm(2) and 723.7 +/- 141.3 mm(2), respectively. At the same heart rate, isoproterenol-treatment resulted in significantly smaller ES and ED areas: 652.8 +/- 146.4 mm(2) and 569.7 +/- 155.9 mm(2), respectively. CONCLUSIONS: The inotropic state of the left ventricle directly affects the mitral valve annular orifice area, independent of heart rate. This inotropic effect on valve size is more pronounced at ED than at ES in the sheep

One-Year Results with a Low-Profile Endograft in Subjects with Thoracic Aortic Aneurysm and Ulcer Pathologies

Objective Evaluate safety and effectiveness of the second generation, low-profile RelayPro thoracic endograft for the treatment of descending thoracic aortic aneurysm or penetrating atherosclerotic ulcer (PAU). Method A prospective, international, non-blinded, non-randomized, pivotal trial analyzed a primary safety endpoint of major adverse events (MAE) at 30 days (death, myocardial infarction, stroke, renal/respiratory failure, paralysis, bowel ischemia, procedural blood loss), and a primary effectiveness endpoint of treatment success at one year (technical success, patency, absence of aneurysm rupture, type I/III endoleaks, stent fractures, reinterventions, aneurysm expansion, and migration) compared to performance goals from the previous generation Relay pivotal study. The study was conducted in 36 centers in the US and Japan and enrolled between 2017 and 2019. Results The study population of 110 patients had a median (IQR) age of 76 (70 – 81) years, n=69 (62.7%) were male, n=43 (39.1%) were Asian, and were treated for 76 fusiform aneurysms (69%), 24 saccular aneurysms (22%), and 10 PAUs (9%). Most patients (82.7%) were treated with a non-bare stent (NBS) configuration. Technical success was 100%: median (IQR) procedure time was 91 (64 – 131) min, deployment time was 16 (10 – 25) min; 50 patients (73.5%) of the US cohort had percutaneous access, while centers in Japan used only surgical cutdown. The 30-day composite MAE rate was 6.4% (95% upper CI 11.6%, p=.0002): 2 strokes, 2 procedural blood losses >1000 mL requiring transfusion, 2 paralysis events, and 1 renal failure. Primary effectiveness was 89.2% (lower 95% CI 81.8%, p=.0185): 9 subjects experienced 11 events (1 aneurysm expansion, 6 secondary interventions, 4 type I endoleaks). There was no loss of stent-graft patency, no rupture, no fractures, and no migration. Conclusions The low-profile RelayPro thoracic endograft met the study primary endpoints and demonstrated satisfactory 30-day safety and 1-year effectiveness for the treatment of patients with aneurysms of the descending thoracic aorta or PAUs. Follow-up is ongoing to evaluate longer term outcomes and durability

TCT-77 Transcarotid Versus Subclavian/Axillary Access for Transcatheter Aortic Valve Replacement: Real-World Comparative Outcomes Utilizing the TVT Registry

Background Transfemoral (TF) access is the preferred delivery method for transcatheter aortic valve replacement (TAVR). Despite advances in TAVR technology, alternative access remains necessary in contemporary practice. Transaxillary/subclavian (TAx) has gained favor as a delivery method, although transcarotid (TC) has become the preferred alternative access for selected sites. Comparison of these approaches has been limited. Methods The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies (TVT) Registry was queried for patients undergoing TC and TAx TAVR with the Sapien 3 (Edwards, Irvine, California) THV from June 2015 through February 2019. Baseline characteristics, unadjusted procedural outcomes, 30-day echocardiography outcomes, length of stay data, and unadjusted 30-day outcomes were evaluated. Results Among the patients undergoing TC and TAx TAVR, there were 2,739 cases. Of these, 17.01% were TC and 82.99% were TAx. Important statistically significant baseline characteristics included baseline STS score (TAx 7.3, TC 7.9; p = 0.008), prior CABG (TAx 23.2%, TC 30.7%; p = 0.0006), prior PCI (TAx 39.8%, TC 45.1%; p = 0.04), and peripheral arterial disease (TAx 65.9%, TC 73.9%; p = 0.0007). Important statistically significant differences in outcome included total procedure time (TAx 131.9 min, TC 122.4 min; p \u3c 0.0001), fluoroscopy time (TAx 21.5 min, TC 17.7 min; p \u3c 0.0001), contrast volume (TAx 97.3 ml, TC 82.7 ml; p \u3c 0.0001) and ICU length of stay (TAx 25.0 h, TC 24.3 h; p = 0.01). The 30-day outcomes had very few statistical differences including mean ejection fraction (TAx 55.6%, TC 57.2%; p = 0.02), and 30-day Kansas City Cardiomyopathy Questionnaire overall summary score (TAx 70.7, TC 67.8; p = 0.03). Stroke rates approached significance (TAx 6.4%, TC 4.2%; p = 0.07), and mortality was comparable (TAx 5%, TC 4.5%; p = 0.68). Conclusion Although TAx delivery has become a dominant alternative access for TAVR, TC offers many benefits as an alternative delivery route. Shorter operative and fluoroscopy times, shorter length of stay, lower contrast volume, and avoiding left internal mammary artery injury or occlusion are clear advantages. Concerns of elevated stroke rates in TC access appear to be unfounded based on these preliminary data. When femoral access is precluded, TC should be considered a viable access strategy compared with TAx access